Jane McNeill is a native of Whiteville, North Carolina, in Columbus County. McNeill first became involved in theater and acting as a sixth grader. She earned a bachelor's degree in journalism from the University of North Carolina at Chapel Hill, but began taking drama classes during her sophomore year at the university. She attended the Eugene O'Neill Theater Center in Connecticut and interned at the Arkansas Repertory Theater in Little Rock following college. McNeill worked as an actor in Wilmington, North Carolina, for one year, and then relocated to Kentucky, where she joined a repertory theater for six months.

In 1990, McNeill moved to Chicago, Illinois, to pursue acting and theater. By her own accounts, she "spent eight years doing theater and waiting tables." McNeill went back to school, earning a master's degree in education from DePaul University. She taught drama and English in the Chicago area until she returned to North Carolina in 1999.

McNeill was diagnosed with breast cancer shortly after returning to Wilmington. Her treatment and recovery put her acting career briefly on hold. In 2012, she told The News Reporter, "I had planned to start auditioning, but by the time we were settled, I learned I had breast cancer...After a year of recovery, acting was at the top of my 'bucket list,' so I started taking classes with casting director Tracy Kilpatrick... Tracy was very instrumental in helping me transition from stage to screen acting... Moreover, she really believed in me and cast me in my first feature film." She signed with a talent agent, Susan Tolar-Walters of STW Talent, during the spring of 2011.

In early June 2011, McNeill was performing in a local play, "The Hallelujah Girls," when she received an email offering her a three-episode audition for the second season of "The Walking Dead." She auditioned for the part of Patricia. Three weeks later, the day before a family trip to New York City, McNeill learned that the role was between either her or a second actress. The next day, McNeill learned she had gotten the part shorty after her plane landed in New York. McNeill's original three-episode role expanded to include the second season. She filmed episodes of "The Walking Dead" every two weeks from July to November 2011. Filming for season two wrapped in November 2011. In December 2011, McNeill began filming "Hornet's Nest," a 2012 TNT television film based on the novel of the same name by Patricia Cornwell, starring Virginia Madsen, Sherry Stringfield, Michael Boatman, Robbie Amell and Quentin Kerr.

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